Oncolytic Adenovirus Coding for Granulocyte Macrophage Colony-Stimulating Factor Induces Antitumoral Immunity in Cancer Patients
- Vincenzo Cerullo1,4,
- Sari Pesonen1,4,
- Iulia Diaconu1,4,
- Sophie Escutenaire1,4,
- Petteri T. Arstila2,
- Matteo Ugolini1,4,
- Petri Nokisalmi1,4,
- Mari Raki1,4,
- Leena Laasonen3,
- Merja Särkioja1,4,
- Maria Rajecki1,4,
- Lotta Kangasniemi1,4,
- Kilian Guse1,4,
- Andreas Helminen1,4,8,
- Laura Ahtiainen1,4,
- Ari Ristimäki4,5,7,
- Anne Räisänen-Sokolowski4,
- Elina Haavisto1,4,
- Minna Oksanen1,4,
- Eerika Karli1,4,
- Aila Karioja-Kallio1,4,
- Sirkka-Liisa Holm1,4,
- Mauri Kouri8,
- Timo Joensuu8,
- Anna Kanerva1,6, and
- Akseli Hemminki1,4
- Authors' Affiliations:1Cancer Gene Therapy Group, Transplantation Laboratory, Haartman Institute and Finnish Institute of Molecular Medicine, 2Department of Bacteriology and Immunology, Haartman Institute, 3Helsinki Medical Imaging Center, University of Helsinki, 4HUSLAB, Helsinki University Central Hospital, Departments of 5Pathology and 6Obstetrics and Gynecology, Helsinki University Central Hospital, 7Genome Scale Biology Program, Biomedicum Helsinki, and 8International Comprehensive Cancer Center Docrates, Helsinki, Finland
- Corresponding Author:
Akseli Hemminki, University of Helsinki and Helsinki University Central Hospital, P.O. Box 63, Haartmaninkatu 8, Helsinki 00014, Finland. Phone: 358-91912-5464; Fax: 358-91912-5465; E-mail: akseli.hemminki{at}helsinki.fi.
Abstract
Granulocyte macrophage colony-stimulating factor (GMCSF) can mediate antitumor effects by recruiting natural killer cells and by induction of tumor-specific cytotoxic T-cells through antigen-presenting cells. Oncolytic tumor cell–killing can produce a potent costimulatory danger signal and release of tumor epitopes for antigen-presenting cell sampling. Therefore, an oncolytic adenovirus coding for GMCSF was engineered and shown to induce tumor-specific immunity in an immunocompetent syngeneic hamster model. Subsequently, 20 patients with advanced solid tumors refractory to standard therapies were treated with Ad5-D24-GMCSF. Of the 16 radiologically evaluable patients, 2 had complete responses, 1 had a minor response, and 5 had disease stabilization. Responses were frequently seen in injected and noninjected tumors. Treatment was well tolerated and resulted in the induction of both tumor-specific and virus-specific immunity as measured by ELISPOT and pentamer analysis. This is the first time that oncolytic virus–mediated antitumor immunity has been shown in humans. Ad5-D24-GMCSF is promising for further clinical testing. Cancer Res; 70(11); 4297–309. ©2010 AACR.
Footnotes
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Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).
- Received September 26, 2009.
- Revision received March 16, 2010.
- Accepted April 8, 2010.
- ©2010 American Association for Cancer Research.
